重症急性肾损伤早期与晚期应用肾脏替代法疗效的Meta分析

Treat severe acute kidney failure with renal replacement therapy in early or late stages-a Meta analysis

目的对比重症急性肾损伤（acute kidney injury,AKI）早期与晚期应用肾脏替代法（renal replacement therapy,RRT）治疗后的生存率与肾功能恢复情况。方法使用Meta分析方法,检索中国知网、万方、MEDLINE、Pub Med、EMBASE、Web of Science（1985年1月至2015年5月）数据库中相关随机对照试验（randomized controlled trial,RCT）及观察性研究文献,并扩展至所有涉及的参考文献,进行双人交叉文献纳入、排除,提取最终获得的文献的效应量,使用STAT11.0进行合并、数据分析。结果获得参考文献1 494篇,经过纳入、排除后,最终获得符合要求的文献15篇（2篇RCT、4篇前瞻队列研究、9篇回顾队列研究）。文献整体方法学质量不高。早期应用肾脏替代法患者比晚期应用患者的28日存活率显著提高（合并OR值=0.45,95%CI：0.28～0.72,P〈0.001）。各研究间异质性较大（I2=78%）。以收治重症加强护理病房（intensive care unit,ICU）类别、研究设计分别进行亚组分析未发现各亚组差异有统计学意义（P〈0.05）。提取有次要结局指标的报道（7篇）的肾功能恢复效应量进行合并,并未发现早期应用比晚期应用肾脏替代法对肾功能恢复有显著提升（OR=0.62,95%CI：0.34～1.13,I2=69.6%）。结论 1）早期应用体外RRT治疗重症急性肾损伤,有助于提高患者存活率,提高幅度明显;2）现有证据表明,早期开展RRT无助于重症AKI患者肾功能恢复;3）提供现有证据的研究大部分样本量较小,研究设计不统一,质量参差不齐。在设计合理的大规模多中心RCT证据出现之前,现有的关于RRT使用时机的结论并不一定能完全代表客观事实;4）有必要展开相关研究,明确定义RRT治疗时机中的＂早期＂与＂晚期＂。

Objective To explore the impact of early versus late initiation of renal replacement therapy（ RRT） on critically ill patients suffered from acute kidney injury（ AKI）. Methods Meta-analysis including effect combination,subgroup analysis and meta-regression were used in the present study. CNKI,WANFANG,Pubmed,EMBASE,SCOPUS and Web of Science（ January 1985 to May 2015） were searched. Cohort and randomized trials that assessed timing of initiation of RRT in critically ill adults with AKI were considered eligible.Results Totally 15 unique studies with 2 randomized,4 prospective cohort and 9 retrospective cohort studies out of 1 494 retrieved citations were identified. The general methodological quality was roughly low. Early,compared with late therapy,was associated with a significant improvement in 28-day mortality [odds ratio（ OR） = 0. 45; 95% confidence interval（ CI） ： 0. 28 to 0. 72,P 〈 0. 001]. There was significant heterogeneity among the 15 pooled studies（ I2= 78%）. In subgroup analyses,stratification was done by（ intensive care unit,ICU） modality or study design,there was no impact on the overall summary estimate for mortality. Early RRT did not; however,it significantly affected the odds of kidney recovery beyond hospitalization（ OR = 0. 62,95% CI： 0. 34 to 1. 13,I2= 69. 6%）. Conclusion1. Earlier institution of RRT in critically ill patients with AKI may have a significant beneficial impact on survival. 2. Merged evidence indicates such beneficial effect cannot be observed for the same population on renal function; 3. Current evidences are basically derived from small sample studies with varied designs and quality. Consequently,any findings about RRT timing cannot be conclusive until new evidence from large-sample,multi-center,sound-design trials have been conducted and reported; 4. Studies focusing on a standardized,plausibledivision between early and late stages of RRT may be particularly necessary.